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Biomedical subjects

R F Miller

Publications and source records attributed to R F Miller.

At least 73 records · Page 4Linked to original sources

Pleural effusions in patients with AIDS.

OBJECTIVE: To describe the range of pathology causing pleural effusions in HIV infected patients with acute respiratory episodes and to attempt to identify whether any associated radiological abnormalities enabled aetiological discrimination. METHODS: Prospective study of chest radiographs of 58 consecutive HIV infected patients with pleural effusion and their microbiological, cytological, and histopathological diagnoses. RESULTS: A specific diagnosis was made in all cases. Diagnoses were Kaposi's sarcoma, 19 patients; para-pneumonic effusion, 16 patients; tuberculosis, eight patients; Pneumocystis carinii pneumonia, six patients; lymphoma, four patients; pulmonary embolus, two patients; and heart failure, aspergillus/leishmaniasis, and Cryptococcus neoformans, one case each. Most effusions (50/58) were small. Bilateral effusions were commoner in Kaposi's sarcoma (12/19) and lymphoma (3/4) than in para-pneumonic effusion (3/16). Concomitant interstitial parenchymal shadowing did not aid discrimination. A combination of bilateral effusions, focal air space consolidation, intrapulmonary nodules, and/or hilar lymphadenopathy suggests Kaposi's sarcoma. Unilateral effusion with focal air space consolidation suggests para-pneumonic effusion if intrapulmonary nodules are absent: if miliary nodules and/or mediastinal lymphadenopathy are detected, this suggests tuberculosis. CONCLUSIONS: A wide variety of infectious and malignant conditions cause pleural effusions in HIV infected patients, the most common cause in this group was Kaposi's sarcoma. The presence of additional radiological abnormalities such as focal air space consolidation, intrapulmonary nodules, and mediastinal lymphadenopathy aids aetiological discrimination.

Acquired Immunodeficiency Syndrome↗

Herpesvirus infection of eye and brain in HIV infected patients.

OBJECTIVES: To compare histological with genome detection methods for diagnosis of herpesvirus infection in eye and brain of HIV infected patients undergoing necropsy and to correlate these findings with both antemortem clinical findings and postmortem evidence of extraocular herpesvirus infection, especially in the CNS. METHODS: A prospective study of 31 consecutive HIV infected patients undergoing necropsy. In life 11 patients had been assessed by an ophthalmologist because of ocular symptoms. Ocular and brain samples were examined for herpesviruses by conventional histological methods and by nested polymerase chain reaction (nPCR) for all eight human herpesviruses; evidence of extraneural herpesvirus infection was sought by histological methods. RESULTS: Although only 12 out of 31 patients (39%) had antemortem clinical evidence of ocular or CNS herpesvirus associated disease, herpesviruses were detected by nPCR in eye and brain from 26 (84%) patients; six patients had more than one herpesvirus infection. There was concordance between ocular and CNS findings in 15 of 19 patients (79%) with CMV infection. 17 of 31 patients (55%) had extraocular or CNS CMV infection at necropsy. Genome detection using nPCR was superior to histological methods for diagnosis of ocular and CNS herpesvirus infection. CONCLUSION: Herpesvirus infection of eye and brain was a frequent finding at necropsy in this group of HIV infected patients; almost a fifth were co-infected by more than one herpesvirus. This was more than twice the incidence predicted from clinical evidence before death. Genome detection using nPCR was superior to histological methods for diagnosis of ocular and CNS herpesvirus infection.

Adult↗

Inferior vena cava filters for HIV infected patients with pulmonary embolism and contraindications to anticoagulation.

OBJECTIVES: To describe the mode of presentation, interventions, and outcome of HIV infected patients with pulmonary embolism and a contraindication to anticoagulation, who were treated with a bird's nest filter. METHODS: Retrospective review of case records and imaging department database at UCL Hospitals, London, UK. RESULTS: Three patients had pulmonary embolism and contraindications to anticoagulation. Contraindications were concomitant intracerebral pathology in two patients (one also had bleeding from gastric Kaposi's sarcoma and the other was cognitively impaired with HIV associated dementia complex) and alcohol induced liver disease/binge drinking in the third patient. Anticoagulation was avoided by introducing a bird's nest filter into the inferior vena cava via the common femoral vein. During follow up (7, 8, and 21 months) no complications or recurrent pulmonary emboli occurred. CONCLUSION: The bird's nest inferior vena cava filter has a role in preventing further pulmonary emboli in HIV infected patients with contraindications to anticoagulation.

Adult↗

Cerebrospinal fluid tau concentrations in HIV infected patients with suspected neurological disease.

OBJECTIVES: To measure cerebrospinal fluid (CSF) tau in HIV infected patients with acute neurological episodes and to correlate the findings with the type and severity of neurological disease. METHODS: CSF tau was prospectively measured in 76 consecutive HIV infected patients admitted to a specialist unit at UCL Hospitals, London, for investigation of acute neurological episodes: the results were compared with the clinical diagnoses. RESULTS: 24 patients had HIV associated dementia complex (HADC), 10 had lymphoma (including four with primary CNS lymphoma), 20 had cerebral infections (including five with CMV encephalitis, five with VZV infection, seven with cryptococcal meningitis, two with toxoplasmosis, and one with progressive multifocal leucoencephalopathy); 22 patients had miscellaneous conditions, including nine with self limiting headache/fever. 62 patients (82%) had normal CSF tau concentration and 14 patients (18%) had elevated tau. In those with HADC, there was no correlation between the degree of dementia or atrophy on magnetic resonance imaging and CSF tau. Elevated CSF tau was associated with poor outcome as six of eight patients who died within 4 weeks of lumbar puncture had elevated tau (p = 0.0024, two tailed Fisher's exact test). CONCLUSIONS: CSF tau levels are not elevated in the majority of HIV infected patients presenting with acute neurological episodes. CSF tau levels show no correlation with severity of dementia/atrophy on magnetic resonance imaging. Although elevated CSF tau was observed in some patients with conditions causing cerebral necrosis, the finding did not delineate underlying pathology but was associated with poor outcome.

AIDS Dementia Complex↗

The network-selective actions of quinoxalines on the neurocircuitry operations of the rabbit retina.

We examined the contribution of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxalole-4-propionic acid (AMPA)/kainate (KA) receptors to the light-responses of rabbit retinal neurons. In the outer retina, bath application of the AMPA/KA receptor antagonists 6,7-dinitro-quinoxaline-2,3-dione (DNQX) and 2,3,dihydroxy-6-nitro-7-sulfamoyl-benzo-f-quinoxaline (NBQX) blocked the light-responses of horizontal cells. Application of quinoxalines enhanced ON-bipolar cell light-responses, and was associated with a hyperpolarization of their resting potentials. In the inner retina, application of both AMPA/KA and NMDA antagonists to AII amacrine-like cells only partially blocked their light-responses. Their residual responses may reflect electrical coupling to neighboring ON-center cone bipolar cells, and can inhibit OFF-center ganglion cells. ON-sustained ganglion cells were highly sensitive to the quinoxalines, which reduced their light-evoked firing, while the firing of ON-transient cells remained as NMDA-mediated light-responses. Quinoxalines had differential effects on the firing rates of ON- and OFF-center ganglion cells: ON-cells were reduced, while OFF-cells were increased. In contrast, firing rates of ON-OFF ganglion cells were not excited by NBQX, and showed a recovered light-response mediated by NMDA receptors. The receptive field surround was lost in ganglion cells. For comparison, NMDA antagonists had only moderate effects on all ganglion cell light-responses. Our results indicate that NMDA and AMPA/KA receptors both contribute to ganglion cell light-responses. However, AMPA/KA receptors also significantly effect the light-response of neurons presynaptic to retinal ganglion cells, altering the observed pharmacology at the ganglion cell level.

Animals↗

Pneumocystis carinii infection in non-AIDS patients.

Infection with the opportunist fungus Pneumocystis carinii remains a significant cause of morbidity and mortality in non-HIV-infected individuals immunosuppressed by a wide range of malignancies, transplantation and inflammatory conditions. Glucocorticoid use appears to be an independent risk factor for the development of Pneumocystis carinii pneumonia. Transmission from infected to susceptible patients may occur, albeit infrequently. A diagnosis of Pneumocystis carinii pneumonia may be achieved in the majority of cases by DNA detection using polymerase chain reaction on oropharyngeal mouth washes.

Journal Article↗

Acute pulmonary embolism in patients with HIV disease.

OBJECTIVES: To determine the incidence, mode of presentation, and outcome of pulmonary embolism (PE) in patients with HIV infection. METHODS: Retrospective review of clinical case records, imaging department database, and necropsy reports of patients admitted to the specialist HIV/AIDS unit at UCL hospitals from April 1993 to August 1997 in order to identify those with a diagnosis of PE. RESULTS: During the study period there were 3792 admissions of whom 10 (0.26%) had PE. All patients with PE presented with fever, seven were dyspnoeic, and seven had cough: all were thought initially to have respiratory infection. Only five patients had pleural pain. All 10 patients had abnormal baseline chest radiographs. The diagnosis in six was made by computed tomograph (CT) pulmonary angiography, in two was made by ventilation perfusion (V/Q) scanning, in one by both techniques, and in one at necropsy. CT angiography in addition to identifying thrombus also showed concomitant lung parenchymal abnormalities in all but one patient. Nine patients with PE had one or more risk factors for venous thromboembolism as did 34/40 case matched controls (odds ratio = 1.67; 95% confidence interval = 0.18-15.5). All patients diagnosed in life were anticoagulated and five survived. CONCLUSIONS: PE was uncommon in this HIV infected population. The diagnosis should be considered in patients with respiratory infection which does not respond to antibiotics. Identifiable risk factors for venous thromboembolism appear to be unhelpful in increasing clinical index of suspicion for PE. As baseline chest radiographs are frequently abnormal, the diagnostic utility of V/Q scanning may be reduced and CT pulmonary angiography is the imaging modality of first choice.

Acute Disease↗

Increased urinary nitric oxide metabolites in patients with multiple sclerosis correlates with early and relapsing disease.

Nitric oxide (NO) has been implicated in the immunopathogenesis of MS as a potential mediator of neuronal loss. To investigate the role of.NO in the development of progressive disease we measured the NO metabolites (nitrate and nitrite) and neopterin, in the urine of 129 patients with demyelinating disease (DD): 23 with clinically isolated syndromes compatible with demyelination and in 46 relapsing remitting (RR) and 60 patients with progressive MS. Eighty-nine of these 129 patients underwent Gd-enhanced MRI. In addition 58 normal control subjects (NC), 19 AIDS and 35 rheumatoid arthritis (RA) patients were studied. Patients with DD, AIDS and RA had significantly elevated urinary nitrate plus nitrite (nit : creat. urine) and neopterin (neopt : creat.urine) to creatinine ratios compared to NC subjects. (Median[25th - 75th%] nit : creat.urine: NC=1183[962 - 1365] vs DD=1245[875 - 2403], AIDS=1686[1231 - 2531], and RA=1950[1214 - 2726] mumol/mol, P<0.001 and median[25th - 75th%] neopt : creat.urine: NC=99[76 - 151] vs DD=163[119 - 266], AIDS=972[653 - 1456], and RA=389[257 - 623] mu mol/mol, P<0.001). Patients with early DD and RR MS had significantly elevated nit : creat.urine compared to patients with progressive MS (nit : creat. urine: 1612[1020 - 2733] vs 1159[790 - 1641] mu mol/mol, P=0.006). The nit : creat.urine and neopt : creat.urine did not correlate with clinical relapse or MRI activity. Excretion of.NO metabolites is increased in patients with early or relapsing-remitting disease.NO appears to be a double-edged sword, mediating tissue damage and modulating complex immunological functions which may be protective in MS.

Acquired Immunodeficiency Syndrome↗